This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular complications account for the vast majority of the mortality and morbidity associated with diabetes (DM). These complications can be broadly categorized as macrovascular and microvascular. Microvascular complications of DM often have devastating effects on the quality of life and survival for patients with diabetes. It is now well recognized that many of microvascular complications are directly related to the degree of hyperglycemia and insulin resistance. However, our understanding of the pathogenesis and appropriate treatment of these disorders is rudimentary. Early detection of microvascular abnormalities will be useful for identifying patients with DM, insulin resistance, or obesity who are at high risk for developing major end-organ complications and who could benefit from therapeutic intervention. A method for routinely assessing microvascular flow reserve could also be useful for early identification of patients with peripheral vascular disease who are candidates for revascularization or other treatments, similar to protocols that are currently employed for the detection of coronary artery disease. Despite the great clinical need, a reliable, non-invasive method capable of assessing perfusion of peripheral tissues at the microvascular or capillary level in patients is currently not available. The overall aim of this proposal is to characterize the microvascular complications are associated with diet induced obesity/insulin resistance in the nonhuman primate (NHP) and that these abnormal responses can be assessed by contrast-enhanced ultrasound (CEU). These studies are using a combination of noninvasive techniques to characterize the level of cardiovascular disease in rhesus macaques chronically consuming a high fat diet.